Clinical evidence
Methotrexate is a well-established medicine with extensive clinical experience in oncology and inflammatory diseases. Current prescribing information includes treatment protocols for acute lymphoblastic leukemia, certain lymphomas, mycosis fungoides and other malignant conditions, as well as rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and severe psoriasis.
A Cochrane systematic review of methotrexate monotherapy for rheumatoid arthritis included seven randomized trials involving 732 participants. Methotrexate produced clinically important improvements in symptoms and physical function compared with placebo and was also associated with a reduction in certain measures of radiographic joint damage.
A large Cochrane network meta-analysis included 158 studies involving more than 37,000 people with rheumatoid arthritis. The evidence supports methotrexate as a key disease-modifying therapy, while combinations with selected conventional or biologic disease-modifying agents can provide additional disease control in patients with an inadequate response to methotrexate alone.
For psoriatic arthritis, a Cochrane review found that low-dose oral methotrexate may provide greater improvement than placebo in treatment response and physical function, although the certainty of evidence was considered low.
Methotrexate has a narrow therapeutic margin and can cause serious toxicity. Current prescribing information highlights risks including severe infections, bone marrow suppression, liver toxicity, pulmonary toxicity, kidney injury, mucosal toxicity and embryo-fetal toxicity. Medication errors involving the dosing schedule can also result in severe or fatal toxicity.
Methotrexate is used as part of treatment for certain malignant diseases, including selected leukemias and lymphomas, as well as other cancers according to specific oncology protocols. At lower doses, it is used as a disease-modifying antirheumatic drug for rheumatoid arthritis and polyarticular juvenile idiopathic arthritis and for systemic treatment of severe psoriasis.
Its mechanism involves inhibition of folate-dependent metabolic pathways and suppression of DNA, RNA and protein synthesis. This particularly affects rapidly dividing cells and, in inflammatory diseases, also reduces abnormal immune activity.
Methotrexate must be taken exactly as prescribed by the treating physician. The dosing schedule depends on the condition being treated. For rheumatoid arthritis and psoriasis, oral methotrexate is commonly administered once weekly, whereas oncology protocols may use different doses and schedules. For rheumatoid arthritis, the U.S. prescribing information lists a starting dose of 7.5 mg once weekly with individualized adjustment; for psoriasis, the recommended oral dose is generally 10–25 mg once weekly until an adequate response is achieved. Oncology dosing is determined by the specific chemotherapy protocol.
The prescribed weekly schedule must never be changed to daily administration without explicit medical instruction. Dosing-frequency errors can cause severe or fatal methotrexate toxicity.
